Background: High grade non-muscle-invasive bladder cancer (HG-NMIBC) is a heterogeneous disease with variable risk of progression. Urinary microRNAs are promising biomarkers for BC detection and surveillance. Let-7c-5p miRNA, clustered with miR-99a-5p and -125b-5p, is deregulated in cancer, including BC. The aim of this study is to evaluate urinary let-7c cluster expression in Ta/T1 HG-NMIBC patients and its impact on progression-free survival (PFS). Methods: Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR) was used to analyze the let-7c cluster expression in 57 urine and 49 neoplastic paired tissue samples prospectively collected from transurethral resection (TUR) HG-NMIBC patients. Twenty urine and 10 bladder tissue samples were collected and analyzed as normal controls. QRT-PCR was also used to detect intra-/extra-cellular let-7c cluster in BC cells. Receiver Operating Characteristic (ROC) curves were used to identify urinary miRNAs cut-off values predicting T-stage and PFS. Uni/multivariable Cox regression was performed to identify predictors of PFS. A nomogram predicting progression risk and a decision curve analysis (DCA) were performed. Results: Urinary let-7c was significantly up-regulated in patients compared with controls, while the whole cluster was down-regulated in tumor tissues. Supporting these findings, in vitro comparison of extra-/intra-cellular ratios of cluster levels between BC cells, showed a higher ratio for let-7c in HG-NMIBC versus low-grade cells. Urinary let-7c cluster expression was increased in higher T-stage and was an independent predictor of progression. Lower EORTC-score and downregulation of urinary cluster were predictors of higher PFS on univariable Cox regression, while on multivariable analysis only cluster expression was an independent progression predictor. On DCA, a benefit was evident for patients with a PFS probability > 20%. Conclusions: Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.

Urinary expression of let-7c cluster as non-invasive tool to assess the risk of disease progression in patients with high grade non-muscle invasive bladder cancer: a pilot study / Spagnuolo, M.; Costantini, M.; Ferriero, M.; Varmi, M.; Sperduti, I.; Regazzo, G.; Cicchillitti, L.; Diaz Mendez, A. B.; Cigliana, G.; Pompeo, V.; Russo, A.; Laquintana, V.; Mastroianni, R.; Piaggio, G.; Anceschi, U.; Brassetti, A.; Bove, A.; Tuderti, G.; Flammia, R. S.; Gallucci, M.; Simone, G.; Rizzo, M. G.. - In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. - ISSN 1756-9966. - 39:1(2020). [10.1186/s13046-020-01550-w]

Urinary expression of let-7c cluster as non-invasive tool to assess the risk of disease progression in patients with high grade non-muscle invasive bladder cancer: a pilot study

Ferriero M.;Sperduti I.;Regazzo G.;Laquintana V.;Mastroianni R.;Anceschi U.;Brassetti A.;Tuderti G.;Flammia R. S.;Gallucci M.;
2020

Abstract

Background: High grade non-muscle-invasive bladder cancer (HG-NMIBC) is a heterogeneous disease with variable risk of progression. Urinary microRNAs are promising biomarkers for BC detection and surveillance. Let-7c-5p miRNA, clustered with miR-99a-5p and -125b-5p, is deregulated in cancer, including BC. The aim of this study is to evaluate urinary let-7c cluster expression in Ta/T1 HG-NMIBC patients and its impact on progression-free survival (PFS). Methods: Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR) was used to analyze the let-7c cluster expression in 57 urine and 49 neoplastic paired tissue samples prospectively collected from transurethral resection (TUR) HG-NMIBC patients. Twenty urine and 10 bladder tissue samples were collected and analyzed as normal controls. QRT-PCR was also used to detect intra-/extra-cellular let-7c cluster in BC cells. Receiver Operating Characteristic (ROC) curves were used to identify urinary miRNAs cut-off values predicting T-stage and PFS. Uni/multivariable Cox regression was performed to identify predictors of PFS. A nomogram predicting progression risk and a decision curve analysis (DCA) were performed. Results: Urinary let-7c was significantly up-regulated in patients compared with controls, while the whole cluster was down-regulated in tumor tissues. Supporting these findings, in vitro comparison of extra-/intra-cellular ratios of cluster levels between BC cells, showed a higher ratio for let-7c in HG-NMIBC versus low-grade cells. Urinary let-7c cluster expression was increased in higher T-stage and was an independent predictor of progression. Lower EORTC-score and downregulation of urinary cluster were predictors of higher PFS on univariable Cox regression, while on multivariable analysis only cluster expression was an independent progression predictor. On DCA, a benefit was evident for patients with a PFS probability > 20%. Conclusions: Urinary let-7c cluster evaluation may improve prognosis, identifying patients at risk of progression and addressing early radical treatment.
2020
let-7c cluster; urinary biomarkers; progression free survival; microRNA; non-muscle-invasive bladder cancer
01 Pubblicazione su rivista::01a Articolo in rivista
Urinary expression of let-7c cluster as non-invasive tool to assess the risk of disease progression in patients with high grade non-muscle invasive bladder cancer: a pilot study / Spagnuolo, M.; Costantini, M.; Ferriero, M.; Varmi, M.; Sperduti, I.; Regazzo, G.; Cicchillitti, L.; Diaz Mendez, A. B.; Cigliana, G.; Pompeo, V.; Russo, A.; Laquintana, V.; Mastroianni, R.; Piaggio, G.; Anceschi, U.; Brassetti, A.; Bove, A.; Tuderti, G.; Flammia, R. S.; Gallucci, M.; Simone, G.; Rizzo, M. G.. - In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. - ISSN 1756-9966. - 39:1(2020). [10.1186/s13046-020-01550-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1408414
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